A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity

Natural killer ( NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally infected cells and tumour cells through the release of cytolytic mediators and interferon ( IFN)-gamma. In humans, blood CD56(dim) NKcells specialize in the lysis of cell targets(1). In the lymph nodes, CD56(bright) NK cells secrete IFN-gamma cooperating with dendritic cells and T cells in the generation of adaptive responses(1,2). Here we report the characterization of a human NK cell subset located in mucosa- associated lymphoid tissues, such as tonsils and Peyer's patches, which is hard- wired to secrete interleukin (IL)- 22, IL- 26 and leukaemia inhibitory factor. TheseNKcells, whichwe refer to as NK- 22 cells, are triggered by acute exposure to IL- 23. In vitro, NK- 22- secreted cytokines stimulate epithelial cells to secrete IL- 10, proliferate and express a variety of mitogenic and anti- apoptotic molecules. NK- 22 cells are also found in mouse mucosa- associated lymphoid tissues and appear in the small intestine lamina propria during bacterial infection, suggesting that NK- 22 cells provide an innate source of IL- 22 that may help constrain inflammation and protect mucosal sites.